THE ROLE OF MITOCHONDRIAL ATP-DEPENDENT POTASSIUM CHANNELS IN THE CARDIOPROTECTIVE EFFECT OF NICORANDIL ON THE MODEL OF CORONARY OCCLUSIVE MYOCARDIAL INFARCTION
The paper presents the results of a study of the antiischemic effectiveness of nicorandil (1,8 mg/kg) on the model of coronary occlusive myocardial infarction in rabbits. The coronary occlusion in the descending branch of the left coronary artery in anesthetized animals was carried out with a 60 minutes ligation followed by a 90 minutes reperfusion. The cardioprotective effect was expressed in 2.5 times restriction of the areas of necrosis, prevention of the increase in the level of Troponin I in 3 times, and the improvement of contractility during the reperfusion. The blocker of ATP-sensitive potassium channels glibenclamide (0.4 mg/kg) almost completely nullified the cardioprotective effects of nicorandil in a dose of 1.8 mg/kg. The inhibitor of inducible NO synthase, aminoguanidine (100 mg/kg), did not cause a complete abolition of the protective effects of nicorandil. The author discusses the priority contribution of ATP-sensitive potassium («first window» of preconditioning) channels in the realization of cardioprotective effects of nicorandil (small and middle dosage), along with no negative hemodynamic effects characteristic of the donor of NO. The latter allows to discuss the possibility of reducing the dose of nicorandil for cardioprotection in clinical studies.
Danilenko LM. The role of mitochondrial ATP-dependent potassium channels in the cardioprotective effect of nicorandil on the model of coronary occlusive myocardial infarction. Research Result. Medicine and Pharmacy Series. 2015;1(4):40-44 (In Russian). DOI: 10.18413 / 2313-8955-2015-1-4-40-44
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